The development of insulin-dependent diabetes mellitus (IDDM) in man, and in animal models of human disease, is characterised by mononuclear cell infiltration and β cell destruction in the pancreatic islets (insulitis). The mechanisms behind β-cell destruction is not known. Accumulating evidence indicates that the cytokines like interleukin-1β (IL-1β), tumour necrosis factor α (TNF-α) or interferon-γ (IFN-γ) or combinations of them, primarily produced by macrophages and monocytes, may be a mediator of islet β-cell destruction [Mandrup-Poulsen T, Nerup J. New concepts in the pathogenesis of insulin-dependent diabetes mellitus. Contrib Nephrol. 1989; 73:1-14; discussion 14-5].
Animal models of human diabetes include diabetes-prone BB (BB-DP) rats and non-obese diabetic (NOD) mice. 2-Dimensional (2D) gel maps of rat islet proteins have been constructed and used to determine qualitative and quantitative changes in protein synthesis resulting with in vitro exposure of rat islet cells to IL-1β (Andersen et al. (1995) Diabetes 44:400-407; John N E et al., Diabetes. (2000); 49:1819-29. Christensen et al., Autoimmunity. (2000); 32:1-15 and Mose Larsen et al., Diabetes. (2001); 50:1056-63). PCT/IB97/01627 describes diabetes-mediating proteins identified by 2-dimensional gel analysis from rats.